Compounds of structure (I) are known and known to have HMG-CoA reductase inhibitory properties. ##STR1## They are the natural fermentation products mevinolin (R=CH.sub.3, U.S. Pat. No. 4,231,938) and compactin (R=H, U.S. Pat. No. 3,983,140) and derivatives thereof all with the natural 2-methylbutyrate side chain. Compounds of structure (II) with the 2,2 dimethylbutyrate side chain and R=CH.sub.3 are known to be more active inhibitors of HMG-CoA reductase than their 2-methylbutyrate analogs. ##STR2## Some compounds of structure (II) and processes for their preparation are disclosed in U.S. Pat. No. 4,444,784 and EPO published application 33538. However the process disclosed therein involves 4 distinct chemical steps: (1) de-esterification of the 2-methylbutyrate side chain; (2) protection of the 4-hydroxy of the pyranone ring; (3) re-esterification to form the desired 2,2 dimethylbutyrate; and (4) deprotection of the 4-hydroxy group. This route was lengthy and gave low overall yields.
U.S. Pat. No. 4,582,915 ("915") disclosed a novel route to the dimethylbutyrate side chain via direct alkylation of the .alpha.-carbon of the naturally available methylbutyrate side chain using a metal alkyl amide and a methyl halide. However this Process has been found to have certain disadvantages in the commercial manufacture of a pharmaceutical. In order to obtain a high conversion of starting material, it was necessary to use a repeat addition of the amide base and methyl halide. This of course exacts a yield penalty and is time-consuming. Furthermore a selective hydrolysis is still necessary to reduce the level of unmethylated starting material to less than 0.7%. This step is time consuming since the hydrolysis of unconverted starting material is very slow and normally requires 20 hours. The overall yield for this process is moderate where the starting material is mevinolin. In addition to unconverted starting material a number of other impurities are generated during the methylation and hydrolysis steps. These include, when the starting material is mevinolin, des-butyratemevinolin and bis-methylated compounds wherein the alpha lactone carbon is methylated in addition to that on the 8 '-C-ester side chain, and a methyl ether wherein the ring oxygen of the lactone now in the open form has been methylated. The purity of the final product isolated from the overall process is close to borderline for use as a human health-care product. A process having a less pronounced impurity spectrum would ensure less chance of batch-to-batch variations causing problems in obtaining acceptable final drug purity without resorting to wasteful repeated recrystallizations.